Sex differences of the shared genetic landscapes between type 2 diabetes and peripheral artery disease in East Asians and Europeans.

Type 2 diabetes (T2D) is a critical risk factor for peripheral artery disease (PAD). However, the sex differences in genetic basis, causality, and underlying mechanisms of the two diseases are still unclear. Using sex-stratified and ethnic-based GWAS summary, we explored the genetic correlation and causal relationship between T2D and PAD in both ethnicities and sexes by linkage disequilibrium score regression, LAVA and six Mendelian Randomization approaches. We observed stronger genetic correlations between T2D and PAD in females than males in East Asians and Europeans. East Asian females exhibit higher causal effects of T2D on PAD than males. The gene-level analysis found KCNJ11 and ANK1 genes associated with the cross-trait of T2D and PAD in both sexes. Our study provides genetic evidence for the sex difference of genetic correlations and causal relationships between PAD and T2D, indicating the importance of using sex-specific strategies for monitoring PAD in T2D patients.